External Potassium Balance Research Articles

Refractory hyperkalemia related to heparin abuse.

Sir, We read with interest the case report of refractory hyperkalemia due to heparin abuse.[1] An effect of heparin is hypoaldosteronism with hyperkalemia caused by direct inhibition of aldosterone biosynthesis and by inhibition of angiotensin-II with secondary hypoaldosteronism.[2,3] In present case hyperkalemia persisted irrespective of calcium gluconate, dextrose insulin, fludrocortisone, salbutamol nebulizers and slow low efficiency renal dialysis.[1] Patient had acidosis, hypotension, septicemia and died of cardiac arrest.[1] The potassium-adenosine triphosphate (K-ATP) is a poor inwardly rectifying channel consisting of pore-forming and sulfonylurea - receptor subunit. The pores confer ATP inhibition while the sulfonylurea receptor is the primary target for sulfonylureas, K-ATP channel openers, and nucleoside diaphosphates.[2] Hypoxia, metabolic acidosis and hypercapnia activates the K-ATP channels, resulting in vasodilatation of coronary, mesenteric, renal and smooth muscle bed and increases potassium efflux and modulates many of the kidney transport functions and maintains external potassium balance.[3] The potency of sulfonylurea drugs in antagonizing vasorelaxant action of K-ATP channel stimulation after the sepsis or endotoxin is well recognized in the laboratory model.[2] Reversal of the life threatening complications of hyperkalemia, vasodilator shock and severe bradycardia by the sulfonylurea inhibitor glibenclamide is a novel approach to the treatment of refractory hyperkalemia.[4] In present case refractory hyperkalemia would have been rectified by glibenclamide.[1,4] The authors working at critical care at tertiary care institute thus could have tried glibenclamide in their case for better outcome.[1,4]

Study of Erythrocyte ATPases in Infants Evaluated during the Recovery Phase of Severe Dehydration Caused by Diarrhea

Background/Aims: Patients severely dehydrated from diarrhea are at risk of developing hyperkalemia consequent to fluid therapy treatment. In parallel with the regulation of external potassium balance by the kidney and gastrointestinal tract, plasma potassium is rapidly regulated by redistribution of potassium between the extracellular and intracellular compartments. Erythrocytes contain ATPases that play a role in this potassium movement. In this study, erythrocyte ATPase effectiveness was evaluated in infants dehydrated from diarrhea and compared to that of healthy infants. Methods: Blood samples were collected from dehydrated and healthy infants. The activity of Na⁺,K⁺-ATPase and of an ouabain-insensitive K⁺-ATPase were assessed. Serum electrolytes and blood pH were also determined. Results: No hyperkalemia was found, even in dehydrated infants presenting with severe hyperchloremic metabolic acidosis. In the erythrocytes of dehydrated infants, Na⁺,K⁺-ATPase activity was increased correlating positively with the amount of sodium administered. High K⁺-ATPase activity in the erythrocytes correlated with low plasma potassium. The K⁺-ATPase activity correlated positively with the amount of potassium administered to dehydrated infants. Conclusion: These findings suggest that the erythrocytes Na⁺,K⁺-ATPase and K⁺-ATPase both protect against plasma potassium abnormalities in dehydrated infants. In such infants, the risk of hyperkalemia is probably low.

Métabolisme du potassium

The intracellular content and the extracellular potassium concentration must remain within narrow limits in order to preserve many cell functions. This chapter describes the mechanisms involved in potassium transfer between extra and intracellular fluids, which are necessary for the maintenance of internal potassium balance, and renal handling of potassium, as well as the regulating factors that are involved in external potassium balance.

Treatment of Potassium Balance Disorders

Potassium is the predominant intracellular cation and is critical for the maintenance of resting cellular membrane potential. Abnormalities of potassium balance can manifest as skeletal and cardiac muscle dysfunction. Abnormalities of potassium concentration in plasma can result from changes in external potassium balance (intake vs. excretion) or internal balance (intracellular to extracellular). Hyperkalemia can result from renal failure, uroperitoneum, or severe dehydration and acidosis in calves with diarrhea. Hypokalemia occurs due to reduced forage intake, when increased gastrointestinal losses occur as with diarrhea, due to increased renal losses as with metabolic alkalosis or exogenous corticosteroid administration which promote kaliuresis, or with redistribution of potassium into the intracellular compartment with alkalosis or in association with insulin-mediated glucose uptake. Aggressive intravenous and oral therapy are often necessary to correct potassium balance disorders, in addition to therapy aimed at correcting any underlying disorder contributing to the potassium imbalance.

Potassium and sodium transport along the loop of Henle: Effects of altered dietary potassium intake

We assessed the effects of changes in potassium (K+) balance on the function of the loop of Henle by a combination of renal clearance and microperfusion experiments. Rat superficial cortical nephrons were perfused in vivo at 20 nl.min-1 from late proximal to early distal tubule with an artificial end-proximal solution containing either 3.8 or 1.8 mM potassium. Rats were fed a control diet, a low-potassium diet for at least three weeks, or a high-potassium diet for 10 to 14 days. When compared with the appropriate end-proximal potassium concentration in the perfusion fluid, potassium absorption along the loop of Henle (JK) increased in potassium-depletion whereas sodium (JNa) and fluid (Jv) absorption decreased. In rats fed a high-potassium diet, absorption of potassium, sodium and fluid was depressed. We propose that changes of external potassium balance affect the transport of electrolytes and fluid along the loop of Henle in vivo by modulating the transport of potassium and sodium primarily in the thick ascending limb. Changes in potassium reabsorption may also be affected by alterations of potassium-recycling.

Potassium supplementation ameliorates mineralocorticoid-induced sodium retention

Potassium depletion induced by dietary potassium restriction causes sodium retention while potassium supplementation augments urinary sodium excretion. The role of external potassium balance in modulating mineralocorticoid-induced sodium retention in humans is unknown. Accordingly, eight healthy subjects were studied at the Clinical Research Center receiving a constant diet providing (per kg body wt) sodium 2.5 mmol, potassium 1.1 mmol daily. After establishing basal sodium and potassium balance over three days, each subject received 9 alpha-fludrocortisone 0.4 mg/day for 10 days. Subjects were studied twice, four to eight weeks apart, in a double blind, randomized crossover design receiving either placebo or additional KCl (80 mmol/day) over the 10 day study period. Serum potassium concentrations were unchanged from basal values on KCl while the values fell (4.1 +/- 0.1 vs. 3.4 +/- 0.1 mmol/liter, P = 0.01) on placebo. Urinary sodium excretion decreased with fludrocortisone administration in both groups, but this decrease reached significance only in the placebo group. Furthermore, during fludrocortisone administration the sodium excretion rates on KCl were significantly higher compared to the values noted on placebo (134 +/- 8 vs. 112 +/- 13 mmol/day, P = 0.01). Body weight recorded after 10 days of fludrocortisone administration was higher on placebo compared to KCl (72.3 +/- 2.8 vs. 71.6 +/- 2.8 kg, P = 0.01). Plasma renin activity, and aldosterone concentrations decreased on fludrocortisone while atrial natriuretic peptide levels increased. These studies suggest that amelioration of hypokalemia attenuates mineralocorticoid-induced sodium retention. Therefore, potassium depletion may contribute to the mineralocorticoid-induced sodium retention.

Urine Electrolytes in the Assessment of Extracellular Fluid Volume Contraction

The purpose of this study was to determine which urine electrolytes should be measured to confirm that the extracellular fluid (ECF) volume is depleted. ECF volume contraction was induced by furosemide administration to rats consuming an electrolyte-free diet. An external potassium balance was achieved by replacing potassium losses with KHCO3 and KCl so that the sodium and chloride deficits were comparable (equivalent to a 30% reduction in ECF volume). As expected, the urine sodium and chloride concentrations fell to 2 +/- 0.3 mmol/l and 3 +/- 0.3 mmol/l, respectively. Rats were then randomized to receive 50-75% of their sodium or chloride deficit as either: NaCl (control group), NH4Cl or NaHCO3 to mimic clinical situations associated with ECF volume contraction. In the NaCl group, the urine sodium and chloride concentrations remained low (6 +/- 2 mmol/l and 7 +/- 2 mmol/l), consistent with persistent ECF volume contraction. Although the NH4Cl group continued to have a low urine sodium concentration (2 +/- 0.2 mmol/l), there was now a marked increase in the urine chloride concentration (51 +/- 7 mmol/l; p less than 0.01 vs. NaCl group). In contrast, although the NaHCO3 group continued to have a low urine chloride concentration (2 +/- 1 mmol/l), there was a significant increase in the urine sodium concentration (19 +/- 3 mmol/l; p less than 0.01 vs. NaCl group). We conclude that the clinical assessment of ECF volume by urine electrolytes requires an evaluation of both the urine sodium and chloride concentrations.

Hyperkalemia: Disorders of Internal and External Potassium Balance

The serum potassium level is normally preserved de spite changes in potassium intake and output (the exter nal potassium balance) and changes in its distribution in the body (the internal potassium balance). External potassium homeostasis depends primarily on renal ex cretion of the daily exogenous potassium burden. Inter nal homeostasis depends on the extrarenal regulation of potassium. Skeletal muscle and liver are the dominant sites of that regulation. The two chief regulators of inter nal balance are insulin and catecholamines, the latter acting through β-adrenergic receptors. Acid-base bal ance and the cellular potassium content are other important regulators of internal balance. The major disorders of external balance are renal failure, hypo reninemic hypoaldosteronism, interstitial nephritis, and a variety of drugs that impair renal potassium excretion. The major disorders of internal balance are diabetes mellitus, acidosis, medications, and release of endoge nous potassium during vigorous exercise, traumatic muscle injury, or tumor lysis chemotherapy. These dis orders frequently result in troublesome elevations of serum potassium in the intensive care setting. Their re view in this article includes a thorough discussion of the evaluation and proper management of the hyperkalemic patient.

Inhibition of furosemide-induced increases in plasma renin activity by amiloride.

The effect of the potassium-sparing diuretic, amiloride, was studied in conscious rabbits bearing chronic indwelling cannulas to assess whether its reported in vitro kallikrein-inhibiting activity may produce a suppressive effect on furosemide-induced renin secretion similar to that previously demonstrated with another kallikrein inhibitor, aprotinin. Furosemide elicited a rapid and persistent rise in plasma renin activity (PRA), but pretreatment of the same rabbits with a 15-minute intravenous infusion of amiloride, which amounted to 1 mg/kg and commenced at 30 minutes before furosemide, completely prevented this rise. Amiloride also prevented furosemide-induced kaliuresis without an attenuation of the diuretic or natriuretic response and did not alter plasma potassium concentration in the absence of any change in external potassium balance, indicating that suppression of the PRA response is due neither to prevention of extracellular fluid volume contraction nor to the known suppressive effect of hyperkalemia. Mean arterial pressure tended to fall slightly but not significantly with or without amiloride pretreatment. On the basis of these findings and those of our antecedent study with aprotinin, we conclude that the striking similarity between the suppressive effects of two dissimilar inhibitors of kallikrein on pharmacologically evoked renin secretion is consistent with the hypothesis that renal kallikrein participates in the mechanism of renin secretion in vivo.

Internal potassium balance and the control of the plasma potassium concentration.

The plasma potassium concentration is determined both by external potassium balance and by the distribution of potassium between extracellular and intracellular fluid compartments, i.e., "internal potassium balance." Whenever external potassium balance is altered, the resultant change in the plasma potassium concentration is strongly influenced by concomitant alterations in internal potassium balance. Several factors alter internal potassium balance independently of changes in external balance. Acid-base disturbances produce shifts of potassium into or out of cells, but attempts to quantify these effects are not likely to be clinically useful. Hypertonicity produces a shift of potassium out of cells. Several hormones (insulin, aldosterone, catecholamines, glucagon, and growth hormone) may have roles in internal potassium balance. Digitalis and succinylcholine, by producing efflux of potassium from cells, may cause hyperkalemia. Potassium is released from skeletal muscle during exercise, causing an increase in the plasma potassium concentration. The periodic paralyses are associated with well-defined transient alterations in internal potassium balance.

The Defense against Hyperkalemia: The Roles of Insulin and Aldosterone

POTASSIUM homeostasis can be conveniently divided into two inter-related systems: external and internal potassium balance. External balance controls total body potassium content and is determined by the difference between potassium intake and potassium excretion. Since potassium losses in the stool and sweat are normally relatively small, renal excretion is the dominant factor that usually determines external potassium balance. In certain kinds of intestinal disorders, however, diarrhea or malabsorption may lead to very large stool losses, but, normally, intestinal excretion plays little or no part in the defense against hyperkalemia. Internal balance refers to the distribution of potassium between the extracellular . . .